J&J's Rybrevant Approved for First-Line NSCLC, Rivaling Tagrisso

Johnson & Johnson recently announced the FDA approval of Rybrevant (amivantamab-vmjw) combined with Lazcluze (lazertinib) for treating locally advanced or metastatic EGFR-mutated non–small-cell lung cancer (NSCLC). This approval marks Rybrevant's second FDA clearance this year and positions the drug to compete directly with AstraZeneca’s Tagrisso (osimertinib), a standard treatment in this category.

The approval is based on results from the Phase III MARIPOSA study, which involved 1074 patients. Participants were randomly assigned to receive either the combination of Rybrevant and Lazcluze or Tagrisso alone. The combination treatment demonstrated a median progression-free survival of 23.7 months, significantly longer than the 16.6 months achieved by Tagrisso alone. While overall survival data are still maturing, the FDA has indicated no negative trends in survival outcomes for the Rybrevant/Lazcluze combination.

Despite this progress, the combination faces challenges, including a serious safety concern related to venous thromboembolic events. As a precaution, the FDA recommends prophylactic anticoagulation for the first four months of treatment. Common side effects reported include rash, infusion-related reactions, musculoskeletal pain, diarrhea, constipation, decreased appetite, and nausea.

The competition between Rybrevant/Lazcluze and Tagrisso is set to intensify. Tagrisso is currently approved both as a monotherapy and in combination with chemotherapy for first-line treatment of EGFR-mutated NSCLC. Dr. H. Jack West, a clinical expert, noted that it would be challenging to replace Tagrisso monotherapy due to Rybrevant's toxicity concerns. Additionally, while Tagrisso offers the convenience of once-daily oral dosing, Rybrevant requires intravenous infusion, which may be a deterrent for some patients and healthcare providers.

However, J&J is developing a subcutaneous version of Rybrevant that could simplify administration. At the American Society of Clinical Oncology (ASCO) annual meeting, J&J presented Phase III trial data indicating that the subcutaneous form of Rybrevant, when combined with Lazcluze, was non-inferior to the intravenous version. This new formulation could reduce infusion-related adverse reactions and significantly decrease dosing times, making the treatment more convenient and potentially more appealing.

Rybrevant’s approval earlier this year in combination with chemotherapy for NSCLC patients with EGFR exon 20 insertion mutations underscores its growing role in J&J’s oncology portfolio. The company aims to address existing administration barriers and enhance patient convenience with upcoming subcutaneous formulations, potentially bolstering Rybrevant's market position.

In summary, while Rybrevant/Lazcluze has made significant strides by demonstrating superior progression-free survival compared to Tagrisso, the combination faces hurdles including safety concerns and the need for intravenous administration. As J&J continues to innovate with a subcutaneous version of Rybrevant, the competition in the first-line treatment of EGFR-mutated NSCLC is poised to become even more dynamic. Whether Rybrevant can achieve its billion-dollar sales potential and displace Tagrisso as the preferred treatment remains to be seen.